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By Amy Norton
-- A particular variant of a cholesterol-related gene may double the risk of Alzheimer's disease in older blacks, a new study suggests.
Still, although a doubling in risk may sound large, the researchers stressed that it's actually a modest increase. Older adults' risk of Alzheimer's is thought to depend on many factors -- not only an array of different genes, but also environmental influences.
"How much does this increase your risk? It's modest," said Dr. Robert Nussbaum, a professor of medicine at the University of California, San Francisco, who was not involved in the study.
But the findings are important because they add to the understanding of the complex underpinnings of Alzheimer's, said Nussbaum, who wrote an editorial published with the study in the April 10 issue of the Journal of the American Medical Association.
The results come from what is believed to be the most extensive search yet for Alzheimer's-linked genes in older blacks.
Most of what is known about Alzheimer's genes has come from data on white adults, because until now there hadn't been a study sample of blacks that was large enough for a gene study, said study lead researcher Dr. Christiane Reitz, an assistant professor of neurology at Columbia University Medical Center in New York City.
Researchers have known for years that whites with a particular variant in the ApoE gene -- called ApoE4 -- have a higher risk of Alzheimer's than whites who carry other variants of the gene.
About 25 percent to 30 percent of the population is thought to carry the Alzheimer's-linked E4 variant.
In the new study, ApoE4 also was linked to an increased Alzheimer's risk among nearly 6,000 blacks aged 60 and older. But the ABCA7 gene was equally important. People with a particular variant of the gene had twice the risk of Alzheimer's as those who carried other variants.
The higher-risk variant was seen in 7 percent of the study participants, Reitz said.
As for what it all means, she said, it's too early to tell.
"This finding needs to be replicated, and we need to learn more about the biological mechanisms," Reitz said.
Like ApoE, the ABCA7 gene is involved in cholesterol metabolism, Reitz said. High cholesterol, heart disease and stroke are considered risk factors for Alzheimer's, and black Americans have higher rates of those cardiovascular problems than whites.
But it's not clear if cardiovascular disease explains why the genes are linked to Alzheimer's -- or why ABCA7 is more important in blacks' risk.
"It's all up in the air," editorial author Nussbaum said. "Gene studies like this are good for finding connections between genes and [disease], but they can't tell us what the mechanisms are."
He said his "gut feeling" is that ApoE and ABCA7 are linked to Alzheimer's independent of their effects on cholesterol and heart disease.
Research has shown that ABCA7 also is involved in transporting amyloid precursor proteins, which help feed the "plaques" that build up in the brains of people with Alzheimer's. That is another potential reason that the gene is linked to Alzheimer's, Reitz said.
But, Nussbaum said, much more research is needed to understand the biology of Alzheimer's. For example, he said, after years of study, researchers are still divided over whether the amyloid plaques in the brains of people with Alzheimer's actually cause the disease.
Reitz said it's too early for people to seek testing for which ABCA7 variant they carry.
You would not be able to run to your doctors' office for such a test anyway -- although there are private companies that offer ApoE testing, Nussbaum said. But that testing is controversial, he said. Many people believe that since there is no known way to prevent Alzheimer's, knowing you have a higher-risk gene will do little good, but potentially create a lot of distress.
On top of that, Reitz said, it is thought that there are probably many gene variants that each increase Alzheimer's risk by a small amount. No single gene variant is the whole story.
Ultimately, Nussbaum said, the hope is that gene studies will help reveal the underlying biological causes of Alzheimer's, and new treatments or preventive measures can be developed.
"The personal, emotional and financial cost of Alzheimer's is huge," Nussbaum said. "It should be a national priority to gain a better understanding of the disease."
It is estimated that about 5 million older Americans have Alzheimer's, and a recent study projected that without any strides in prevention, that number will triple by 2050.
"If we could figure out ways to delay Alzheimer's by even five years, that would have a big impact," Nussbaum said.
The study was funded by grants from the U.S. government, the Alzheimer's Association and drug maker GlaxoSmithKline. Nussbaum has financial ties to Complete Genomics, a company that does gene sequencing for researchers.
Learn more about Alzheimer's genes from the U.S. National Library of Medicine.
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